At the beginning of the 20th century, around one in three children in countries such as Australia and the United States died of infection before the age of five. But since Howard Florey first described the power of penicillin in 1947 and antibiotics became widely available, we have come to expect that life-threatening bacterial infection can be easily managed.
Early antibiotic therapy still means the difference between life and death for a previously healthy young person with a severe blood infection. However, we have long known that bacteria can quickly adapt to overcome the antibiotics that used to kill them. These antibiotic-resistant bacteria are often referred to as “superbugs”.
From common bacteria to superbug
Many disease-causing bacteria are only occasional visitors to our body, quietly coming and going. These visitors sometimes cause severe infection: the classic example is the golden staph (Staphylococcus aureus), which we seek to control with hygiene measures such as hand washing to prevent transmission, and antibiotics to treat infection.
We know that major genetic mutations in bacterial populations are rare, as in most populations, but these bacterial communities are huge. Like Darwin’s finches, changes tend to take over a population if they enhance biological success.
Subtypes of golden staph developed the capacity to survive antibiotics soon after they met them. Antibiotic-resistant variants of golden staph such as Methicillin Resistant Staphylococcus aureus (or MRSA) cause skin, bone and joint, and soft tissue infections (abscesses) and occasionally lethal blood poisoning (septicaemia). These resistant golden staph are now very common, both in hospitals and in the community.
Other bacteria work differently. Escherichia coli (E. coli), and bacteria like it, exist as permanent populations in our own gut ecosystem, where they are specifically adapted to live. Most strains of E. coli are harmless, but some can cause food poisoning, urinary tract infections (UTIs) and other serious infections.
Bacteria like E. coli have always exchanged advantageous genes quickly and efficiently, sharing a big gene pool. The genes move around mostly in specialised packages called plasmids, which shuttle between bacteria. This system provides the bacteria with an enormous capacity to adapt to change.
It’s not surprising then, that this gene pool now includes many antibiotic-resistance genes on plasmids. This process of pick-up of a resistance plasmid from the gene pool takes only minutes and can even occur during treatment.
So, what does this mean for us? If an E. coli spills into the bloodstream from a simple urinary tract infection, the infection can usually be treated with modern antibiotics, even if the infection overwhelms the body, as in cases of septic shock. However, if that E. coli can obtain a resistance plasmid and overcome the antibiotics, even the best intensive care treatment may not be able to save the patient’s life.
The threat from within
While MRSA was the superbug of the recent past, the biggest future threat may be from species that are part of our own normal ecology, such as E. coli. This gene pool story is the main reason.
To understand it, you might think of the gut as like a rainforest, home to a diverse range of flora (the bacterial “microflora”). But just as weed species can threaten a rainforest, plasmids carrying resistance genes can dominate the gut’s bacterial gene pool.
In this ecosystem, resistance plasmids and related (non-resistant) plasmids compete for ecological turf. These plasmids are designed to “stick” in bacteria and once in, tend to be permanent – staying long after the antibiotics are gone.
This is the nub of the problem. Because disease-causing strains are more likely than their harmless cousins to be treated with antibiotics, they are more likely to have resistance plasmids.
It’s therefore logical to expect antibiotics to help disease-causing sub-populations to flourish within each bacterial species. This should be true for E. coli and all bacteria like it (such as Klebsiella, Salmonella).
So, if this is generally how things work, does this mean that we’ll all be at greater risk of untreatable food poisoning and UTIs in future? The short answer is yes. This is the natural response of an ecosystem (in this case, the bacteria of the human gut) to selection pressure (in this case, antibiotic exposure).
It’s important to note that the battle between resistant and naturally occurring bacteria isn’t just happening within our own guts – we share our gut bacteria with humans and animals all over the world. So antibiotic exposure in one place leads to antibiotic resistance in another.
Here in Australia, E. coli infection responds to standard hospital-type antibiotics more than 19 times out of 20, while in India this may be only one in three. These two figures may well come closer together over time.
We need to think of the human (and animal) gut microflora as an inter-connected global ecosystem, and ask ourselves if we are managing it well. If we remain heedless of this risk, we may pass a tipping point beyond which this vital ecosystem, the gut microflora, cannot recover.
Thankfully, rapid advances in our understanding of microbial ecology and gene transmission should allow us to manage and possibly even restore this ecosystem. As long as we act in time.
This is the second article in Superbugs vs Antibiotics, a series examining the rise of antibiotic-resistant superbugs. Click on the links below to read the other instalments.
Part nine: New antibiotics: what’s in the pipeline?